The present invention relates to a hydrophobic polymer dispersion according to the preamble of claim 1.
Such a dispersion contains modified starch dispersed in a liquid phase together with admixtures which are used in dispersions and known as such.
The invention also relates to a process according to the preamble of claim 16 for the formation of a hydrophobic polymer dispersion.
The emphasis on an environmentally friendly attitude and green values is opening up new markets for products based on renewable natural resources. Such trends are emerging in the fields of, among others, the packing industry, the sanitary product industry and the adhesive industry, where recyclability, reuse, compostability, biodegradability and lack of environmental stress are demands of today. The trend of replacing products based on petrochemistry by processed biopolymer products is also accentuated. Starch and its derivatives constitute a particularly interesting starting material for the production of biodegradable polymer products.
Polymer dispersions are used, e.g., to coat paper and board so as to improve their water resistance. In addition to fillers, dispersions used within the paper industry today also contain various synthetic latexes which are quite poorly decomposed in a biological environment.
Solutions are previously known in which modified starch components are used for the preparation of paper coating dispersions. Thus, a coating composition is known from WO Published Application No. 93/11300, based on a polymer dispersion containing a starch derivative having a polymer grafted thereto containing styrene and butadiene monomers. Therefore. this solution makes no use of such biodegradable components which are compatible with the demands on recyclability set on the products.
The present invention aims at achieving a hydrophobic dispersion most or preferably essentially all of whose components are biodegradable. The invention particularly aims at producing a dispersion whose polymer component mainly comprises a biodegradable polymer, advantageously starch or a derivative thereof. Furthermore, the invention seeks to provide a process for the production of hydrophobic dispersions.
The invention is based on the surprising observation that many biodegradable polymers can advantageously be dispersed in water by first plasticizing them and by dispersing the plasticized melt in water using dispersion admixtures. Thereby no solvents are required for producing the dispersion. Thus, according to the present process,
as the polymer, a biodegradable polymer is used, first mixed with a plasticizer in order to obtain a plasticized blend,
the blend is mixed with admixtures and water in optional order so as to obtain a dispersion, whereby the mixing is carried out at an elevated temperature, and
if desired, the dispersion is homogenized.
In more detail, the dispersion according to the invention is mainly characterized by what is stated in the characterizing part of claim 1.
The process according to the invention. then, is characterized by what is stated in the characterizing part of claim 16.
The invention provides considerable benefits. Thus, the base materials of the starch dispersion according to the invention are mainly based on renewable natural resources and are biodegradable/compostable. The starch component may be derived from any native starch: it need not be, e.g. a starch rich in amylose. No solvents requiring removal by evaporation are needed for the formation of the dispersion instead, the dispersion may be carried out by means of a melt processing apparatus, whereby the consumption of plasticizer is simultaneously considerably reduced. The films formed from the dispersion have a high water repellence and can be used to improve the water resistance of paper or board by at least 40 to 50%.
The new polymer dispersions may be used for coating paper or board, as a primer or as a component in labelling adhesives or paint. They are also suited for the production of hydrophobic cast films and for use as binders in materials based on cellulose fibres.
A particularly interesting embodiment comprises use of polymer dispersions for coating, for instance, medicinal preparations in tablet form.
The coating of medicinal preparations in tablet form is as such a very commnon process within the pharmaceutical industry. The purpose of the coating is either to cover the disagreeable taste or smell of the drug, to protect the drug against external factors during storage or dosage, to facilitate the packaging, identification or dosage of the tablets, or to control the release of active substance from the tablet. The most demanding ground for coating pharmaceutical tablets is the aim of obtaining controlled, usually retarded release of the active substances. The purpose is to achieve a desired rate of absorption by the body of the active substance over a longer time span. The purpose may, however, even lie in achieving the release and absorption of an active substance in a certain part of the digestive tract, this being the optimal part for the absorption of the medicinal preparation in question.
As a pharmaceutical process, the coating of tablets with a polymer film is carried out by spraying a solution or dispersion containing the coating polymer onto the tablets and by then evaporating the solvent or medium by means of pressurized air. Traditionally, polymers dissolved in organic solvents have been used for coating tablets containing medicinal preparations. Typical examples comprise ethyl cellulose and hydroxypropyl methyl cellulose. During the past few years, this technology has been developed especially for water-based coatings. In such a case the coating polymer is either soluble in water or dispersible in water. Polymers which are dispersible in water offer a wider range of possible uses from the point of view of controlling the release of active substances than do those soluble in water. Ethyl cellulose, among others, is available in the form of aqueous dispersions.
The use of aqueous dispersions is aimed at because organic solvents are environmentally less friendly and cause more problems for those dealing with them at work. The change is, however, not entirely free from complications, because the elaboration of dispersion processes is most demanding and not nearly all of the currently used polymers can be used to yield a dispersion. Furthermore, industrial processes for the preparation of drugs often have such dissimilar details that the same coating methods and equipment cannot be used in all cases. In addition, the properties of polymer films made from aqueous dispersions are often essentially different from those of films made from organic solutions.
The present invention can be used to obtain polymer dispersions particularly suited for coating pharmaceutical preparations. The dispersions are especially well suited for coating solid pharmaceutical preparations, such as pharmaceutical preparations with prolonged effect. As examples of pharmaceutical preparations subjected to coating, tablets, capsules and pellets may be cited, as well as particle-shaped drug carrier and allocator systems, such as nanoparticles, nanocapsules, microparticles, and colloidal dispersions. The release rate of a pharmaceutical substance may be controlled by regulating the thickness of the polymer film formed. By modifying the dispersion formulation, an optimal release profile for the medicinal preparation is easily obtained.
The invention is examined in more detail in the following in the light of a detailed description and a number of working examples.
The annexed FIGURE is a graphic pesentation of the release of active substance from dicalcium phosphate tablets coated with dispersions according to the present invention.
Hydrophobic starch dispersions can be produced by means of the process described herein. containing as the starch component a starch ester, starch ether, mixed ester/ether of starch or grafted starch made from native starch, hydrolyzed starch, oxidized starch, crosslinked starch, or gelatinized starch. Hydrophobic polymer dispersions can also be prepared form other biodegradable polymers such as polycaprolactone, lactic acid polymers, polylactide and/or polyhydroxyburyrate/-valerate. The last mentioned polymers can naturally be used in mixtures with starch polymers. Most advantageously, hydrophobic starch ester containing polymer dispersions are obtained.
In the composition according to the invention, starch or a derivative thereof, in the following also called starch component. may be based on any native starch having an amylose content of 0 to 100% and an amylopectin content of 100 to 0%. Thus, the starch component may be derived from barley, potato, wheat, oat, pea, corn, tapioca, sago, rice, or a similar ruber-bearing or grain plant. It may also be based on starches prepared from said native starches by oxidizing, hydrolyzing, crosslinking, cationizing, grafting, etherifying or esterifying.
It has proved advantageous to use a starch-based component derived from an ester formed by starch and one or several aliphatic C2-24 carboxyl acids. The carboxyl acid component of such an ester may then be derived from a lower alkane acid, such as acetic acid, propionic acid or butyric acid, or a mixture thereof. The carboxyl acid component may, however, even be derived from a saturated or an unsaturated native fatty acid. Examples of these include palmitic acid, stearic acid, oleic acid, linoleic acid, and mixtures thereof. The ester may also also consist of both long- and short-chain carboxyl acid components. As an example, a mixed ester of acetate and stearate may be cited.
The preparation of fatty acid esters of starch is carried out. for example, in the manner described in the publications Wolff, I. A., Olds, D. W. and Hilbert, G. E., The acylation of Corn Starch, Amylose and Amylopectin. J. Amer. Chem. Soc. 73 (1952) 346-349, or Gros, A. T. and Feuge. R. O., Properties of Fatty Acid Esters of Amylose, J. Amer. Oil Chemists"" Soc 39 (1962) 19-24.
Starch acetates can be prepared by allowing the starch to react with an acetanhydride in the precence of a catalyst. As catalyst, a 50% sodium hydroxide is used, for example. Even the other known processes for the preparation of acetates are suited for the preparation of starch acetate. By varying the amount of acetic acid anhydride, the amount of the base used as catalyst as well as the reaction duration, starch acetates with different degrees of substitution may be prepared.
The starch component is advantageously an esterified starch, preferably a starch acetate with a degree of substitution between 0.5 and 3, advantageously 1.5 and 3 and most suitably 2 and 3. It is particularly preferred to use, e.g., enzymatically hydrolyzed barley starch for the preparation of starch esters.
As stated above, the starch component is given a plastic form by admixing it with a softening agent or plasticizer known as such. For this purpose, the dispersion composition according to the invention is made to contain preferably 0.01-95% by weight, advantageously about 1-50% by weight of plasticizer. Any known plasticizers can be used, such as triacetin, diacetin, monoacetin, triethyl citrate, tributyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, dimethyl succinate, diethyl succinate, ethyl lactate, methyl lactate, fatty acid esters of glycerol, castor oil, olive oil. rapeseed oil, tall oil, dibutyl phthalate, diethyl phthalate, and mixtures thereof.
The starch dispersion further contains a dispersion admixture which allows for the dispersion of the plasticized polymer melt in sufficiently fine particles in water so as to form a stable dispersion. As an example of dispersion admixtures, polyvinyl alcohol (PVA) may be cited, in particular PVA whose weight-average molar mass is about 10,000 to 115,000. Other dispersion admixtures (protective colloids) include cationic starch and hydroxyalkyl starch, whereby these can be used separately or together with PVA. The dispersions may further contain alkyl-ketene dimer (AKD) wax and beeswax as additives or admixtures.
As an example of advantageous polymer dispersion compositions, a composition may be cited containing
5 to 25 parts by weight of a starch ester,
5 to 50 parts by weight of a plasticizer,
1 to 150 parts by weight of water, and
1 to 20 parts by weight of a dispersion admixture.
Typically, water is present in an amount which is 2 to 10 times, preferably about 4 to 6 times, and plasticizer in an amount which is about 0.1 to 2 times, and admixture in an amount which is about 0.1 to 1.5 times the amount of the biodegradable polymer. Thus, as regards, for example, the preparation of a hydrophobic starch ester dispersion, it can be cited that about 1.0 to 5 kg of starch ester, 0.5 to 6 kg of plasticizer, and about 0.1 to 1.5 kg of admixture may be dispersed in 10 kg of water.
Depending on the intended use, such a polymer dispersion may even be made to include 0.01 to 30% by weight, preferably about 5 to 30% by weight of a cellulose ester, such as cellulose acetate. cellulose propionate or cellulose butyrate, or mixed esters theraof.
The present dispersion compositions are prepared by dispersing a plasticized polymer melt in water with the aid of admixtures. In order to achieve plasticizing, the biodegradable polymer is admixed with the plasticizer suitably at an elevated temperature so as to form a melt. On a small scale, the plasticizing may be carried out in, e.g., a flask equipped with a reflux condenser and efficient mixing. The temperature varies according to the plasticizer used but is typically about 50 to 250xc2x0 C., preferably about 100 to 200xc2x0 C. On a larger scale, the plasticizing is advantageously carried out in a melt processing apparatus, such as an extruder.
The plasticized melt is dispersed in liquid phase, usually water, using admixtures. Water is a particularly preferred dispersion medium according to the invention, but the invention may also be applied such that various solvents are used.
The admixture and water may be added in optional order, Thus, the admixture may first be added to the plasticized polymer melt, whereafter the water or admixture may be dissolved in water and added along with the water. In both cases, a gradual addition of water is preferred. Most suitably, the addition of water and admixture is performed with a velocity allowing the mass to remain homogeneous without any separation of phases. According to an advantageous embodiment. this is achieved by bringing water in drops or otherwise in small quantities into the hot plasticized biopolymer, e.g., a starch derivative or starch, by means of a pump. During the addition, the condensing of the evaporating water is seen to, whereafter it is brought back into the mixture. When starch-based dispersions are prepared, it is particularly beneficial to first add a small amount of water dropwise into the molten mass, and the addition is interrupted for some time, typically 5 to 30 minutes, so as to make sure that the mass is well mixed and homogeneous. Next, the adding of water dropwise can be continued until all of the water has been added. In the case of other biodegradable polymers, water can be added without interruptions.
According to one advantageous embodiment, the dispersion is prepared by
admixing 5 to 25 parts by weight of a starch ester with 5 to 50 parts by weight of a plasticizer so as to obtain a plasticized starch ester mixture,
keeping the liquid phase at a temperature of about 100 to 180xc2x0 C. during mixing, and
adding 1 to 150 parts by weight of water and 1 to 20 parts by weight of a dispersion admixture into the plasticized starch ester mixture, whereby the liquid phase is kept at a temperature of about 50 to 100xc2x0 C. while adding the water.
According to another particularly advantageous embodiment the dispersion is prepared by intermixing in a polymer melt processing machine at 100 to 250xc2x0 C.
5 to 25 parts by weight of a starch ester,
5 to 50 parts by weight of a plasticizer,
1 to 20 parts by weight of an admixture for forming a plasticized starch ester blend, and by
admixing the plasticized starch ester blend into 1 to 150 parts by weight of water at a temperature of about 50 to 100xc2x0 C. in order to form a hydrophobic dispersion.
The dispersion can, however, also be carried out by mixing the admixture with water and by merely intermixing the starch ester and plasticizer in the melt processing machine.
After dispersing, the dispersion is, if desired, homogenized in a manner known per se in order to stabilize it. Homogenization can, for instance, be achieved by means of a pressure homogenizer. As will emerge from Example 2, homogenization can be used to reduce particle size by 50 to 100%, thus improving the stability of the dispersion. Dispersions according to the invention will remain stable for several weeks, even months.
The invention can be used to obtain dispersions of biodegradable polymers, preferably starch derivatives, in particular starch esters, with 90% of the polymer particles smaller than 10 xcexcm. By homogenizing, dispersions are obtained with average particle sizes below 2 xcexcm or even below 1 xcexcm. According to the intended use, dispersions can father be prepared with a multimodal, in practice usually bimodal, particle size distribution.